Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High-dose estrogen administration induces anemia in mammals. In chickens, estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation. This delay is associated with down-regulation of many erythroid cell-specific genes, including alpha- and beta-globin, band 3, band 4.1, and the erythroid cell-specific histone H5. We show here that estrogens also reduce the number of erythroid progenitor cells in primary human bone marrow cultures. To address potential mechanisms by which estrogens suppress erythropoiesis, we have examined their effects on GATA-1, an erythroid transcription factor that participates in the regulation of the majority of erythroid cell-specific genes and is necessary for full maturation of erythrocytes. We demonstrate that the transcriptional activity of GATA-1 is strongly repressed by the estrogen receptor (ER) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen. ER-mediated repression of GATA-1 activity occurs on an artificial promoter containing a single GATA-binding site, as well as in the context of an intact promoter which is normally regulated by GATA-1. GATA-1 and ER bind to each other in vitro in the absence of DNA. In coimmunoprecipitation experiments using transfected COS cells, GATA-1 and ER associate in a ligand-dependent manner. Mapping experiments indicate that GATA-1 and the ER form at least two contacts, which involve the finger region and the N-terminal activation domain of GATA-1. We speculate that estrogens exert effects on erythropoiesis by modulating GATA-1 activity through protein-protein interaction with the ER. Interference with GATA-binding proteins may be one mechanism by which steroid hormones modulate cellular differentiation.
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PMID:Ligand-dependent repression of the erythroid transcription factor GATA-1 by the estrogen receptor. 776 Aug 10

A phase II study to test the toxicity and the efficacy of a weekly combination of Mitoxantrone, 5-Fluorouracil and L-Leucovorin (MFL) was carried out in 43 patients with metastatic breast cancer. Chemotherapy consisted of mitoxantrone 4 mg/m2, 5-fluorouracil 375 mg/m2, and L-leucovorin 100 mg/m2 on day 1, weekly. Patient characteristics were: median age 53 years (range 36-65); estrogen receptor (ER) status was known in 26 patients and of these 15 (57.7%) patients were ER-positive and 11 (42.3%) ER-negative. Of the 43 patients, 25 (58.1%) and 18 (41.9%) patients had received prior adjuvant chemotherapy and prior adjuvant endocrine treatment, respectively. MFL was administered to 22 (51.1%) patients as first line chemotherapy for advanced disease, while 21 (48.9%) patients had received 1 to 2 cytotoxic regimens for metastatic disease. The dominant sites of metastases were: soft tissue in 11 (25.5%) patients, bone in 8 (18.6%) patients and viscera in 24 (55.9%). All patients were assessable for toxicity: only 8 patients experienced WHO grade 3 leukopenia. Thrombocytopenia, diarrhea, stomatitis, and nausea/vomiting were negligible. Anemia and alopecia were not observed. Thirty-nine patients were assessable for response: overall response rate was 28.2% (complete response 7.7% and partial response 20.5%). Median duration of response was 12 months (range 6-34). Patients with no prior anthracyclines had a 42.1% response rate compared to 15% in patients who had received anthracyclines. Median overall survival of the 43 patients was 6 months (range 1-34). Weekly MFL is a well-tolerated and a moderately effective regimen for the treatment of metastatic breast cancer.
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PMID:Phase II study of weekly mitoxantrone, 5-fluorouracil, and leucovorin in metastatic breast cancer. 794 11

A late phase II study of CPT-11 for advanced breast cancer was conducted at 27 institutions. Seventy-nine patients were enrolled, 75 were eligible for the study, and 65 were evaluable for efficacy. One complete response and 14 partial responses were obtained, and the response rate was 23%. The response rate of patients with prior endocrine therapy and prior chemotherapy including adriamycin or other anthracycline drugs was 27% (11/41) and 26% (12/46), respectively. The response rate for patients with estrogen receptor-negative tumors and premenopausal patients was 32% (6/19) and 27% (4/15), respectively. Responses were observed not only for soft tissue lesions such as lymph nodes (5/17), but also for distant metastases in the lungs (8/28) and bone (1/18). The major adverse reactions were myelosuppression and gastrointestinal symptoms. The incidence of Grade 2 or higher leukopenia, anemia, nausea/vomiting, anorexia, diarrhea and alopecia was 68%, 31%, 67%, 59%, 37%, and 30%, respectively. These results suggested that CPT-11 was a promising drug for advanced breast cancer.
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PMID:[A late phase II study of CPT-11 (irinotecan) in advanced breast cancer. CPT-11 Study Group on Breast Cancer]. 821 Feb 51

The clinical, gross, microscopic, and immunohistochemical features of four examples of exceedingly rare uterine angiosarcomas reviewed at the Armed Forces Institute of Pathology between 1970 and 1997 are presented. One of the cases described has been reported previously. Based on our findings and a review of the literature, uterine angiosarcomas are aggressive lesions that occur predominately in peri- and postmenopausal women with uterine bleeding and anemia. Grossly, the lesions are of large size at initial presentation with deep myometrial extension. Histologically, the lesions demonstrate characteristic features of angiosarcoma and, when associated with a benign smooth muscle proliferation within the uterus, tend to demonstrate an epithelioid morphology. The immunohistochemical reactivity with CD31, factor VIII, and CD34 and lack of reactivity with smooth muscle actin, keratin, and estrogen receptor confirm the vascular nature of these lesions and exclude the differential diagnostic considerations of carcinosarcoma (MMMT), leiomyosarcoma, adenosarcoma, and hemangiopericytoma. The overall survival of these lesions is poor; the majority of women die of disease within 1 year of diagnosis.
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PMID:Uterine angiosarcomas: a morphologic and immunohistochemical study of four cases. 950 Feb 27

A phase II trial was designed to evaluate the effectiveness of docetaxel/cisplatin as primary or neoadjuvant chemotherapy of locally advanced breast carcinoma (LABC). Patients with newly diagnosed breast cancers > or = 5 cm in size by palpation were treated with docetaxel/cisplatin, both at 70 mg/m2 intravenously every 21 days for 4 courses. Upon completion of chemotherapy, all patients underwent modified radical mastectomy with axillary nodal dissection. Pathologic complete response (pCR) was defined as absence of any invasive carcinoma in the breast. Standard AC (doxorubicin/cyclophosphamide) at 60 mg/m2 and 600 mg/m2, respectively, for 4 cycles was given as adjuvant therapy to maximally eradicate occult distant disease. Between March 1998 and October 2001, 57 women were entered onto this trial, 28 (49%) with inoperable T4 and inflammatory cancers. Pretreatment median tumor size was 9 cm. Thirty-six patients (63%) had estrogen receptor-positive tumors and 10 patients (18%) had tumors with HER2 overexpression. All tumors became operable after neoadjuvant chemotherapy. Pathologic complete response in the breast was achieved in 15 patients (26%) and pCR in the breast and the axilla was achieved in 11 patients (20%). All neoadjuvant chemotherapy courses were administered at full doses without treatment delays caused by toxicity. The most common side effects were hyperglycemia, anemia, and mild neuropathy. The results of this study suggest that the docetaxel/cisplatin combination can be an effective and well-tolerated induction treatment of LABC, even in very large mostly HER2-nonoverexpressing tumors.
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PMID:Docetaxel and cisplatin as primary chemotherapy for treatment of locally advanced breast cancers. 1558 76

Chicken anemia virus (CAV) is a small circular single-stranded DNA virus with a single promoter-enhancer region containing four consensus cyclic AMP response element sequences (AGCTCA), which are similar to the estrogen response element (ERE) consensus half-sites (A)GGTCA. These sequences are arranged as direct repeats, an arrangement that can be recognized by members of the nuclear receptor superfamily. Transient-transfection assays which use a short CAV promoter construct that ended at the transcription start site and drive expression of enhanced green fluorescent protein (EGFP) showed high basal activity in DF-1, LMH, LMH/2A, and primary theca and granulosa cells. The estrogen receptor-enhanced cell line, LMH/2A, had significantly greater expression than LMH cells, and this expression was significantly increased with estrogen treatment. A long promoter construct which included GGTCA-like sequences downstream of the first CAV protein translation start site was found to have significantly less EGFP expression in DF-1 cells than the short promoter, which was largely due to decreased RNA transcription. DNA-protein binding assays indicated that proteins recognizing a consensus ERE palindrome also bind GGTCA-like sequences in the CAV promoter. Estrogen receptor and other members of the nuclear receptor superfamily may provide a mechanism to regulate CAV activity in situations of low virus copy number.
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PMID:Positive and negative regulation of chicken anemia virus transcription. 1570 5

Treatment approaches for early breast cancer continue to evolve as key trials involving adjuvant chemotherapy and hormonal therapy provide results that can inform clinical practice. The administration of a taxane, either in combination with or following doxorubicin and cyclophosphamide, has been shown to significantly improve disease-free survival (DFS) and overall survival (OS). In addition, a dose-dense treatment approach (reducing the inter-treatment interval) was found to be more effective than conventionally scheduled treatment in terms of DFS and OS. As treatment schemes evolve, supportive care becomes increasingly important to manage the toxicities of chemotherapy, such as anemia and impaired cognition. In addition to chemotherapy, the use of hormonal therapy continues to evolve, with studies demonstrating the benefit of the aromatase inhibitors and serum estrogen receptor down-regulation.
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PMID:Evolving treatment approaches for early breast cancer. 1577 May 34

Erythroid Kruppel-like factor (EKLF, KLF1) plays an important role in definitive erythropoiesis and beta-globin gene regulation but failure to rectify lethal fetal anemia upon correction of globin chain imbalance suggested additional critical EKLF target genes. We employed expression profiling of EKLF-null fetal liver and EKLF-null erythroid cell lines containing an inducible EKLF-estrogen receptor (EKLF-ER) fusion construct to search for such targets. An overlapping list of EKLF-regulated genes from the 2 systems included alpha-hemoglobin stabilizing protein (AHSP), cytoskeletal proteins, hemesynthesis enzymes, transcription factors, and blood group antigens. One EKLF target gene, dematin, which encodes an erythrocyte cytoskeletal protein (band 4.9), contains several phylogenetically conserved consensus CACC motifs predicted to bind EKLF. Chromatin immunoprecipitation demonstrated in vivo EKLF occupancy at these sites and promoter reporter assays showed that EKLF activates gene transcription through these DNA elements. Furthermore, investigation of EKLF target genes in the yolk sac led to the discovery of unexpected additional defects in the embryonic red cell membrane and cytoskeleton. In short, EKLF regulates global erythroid gene expression that is critical for the development of primitive and definitive red cells.
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PMID:A global role for EKLF in definitive and primitive erythropoiesis. 1638 Apr 51

Tamoxifen (TAM) is a nonsteroidal antiestrogen that prevents estrogen receptor-positive breast cancer in rodents and humans. Bexarotene (BEX), a selective agonist for retinoid X receptors, inhibits mammary carcinogenesis in rodents. The present study was conducted to support the preclinical development of TAM (tamoxifen citrate) + BEX for use in breast cancer chemoprevention, and to investigate the influence of these agents on hepatic gene expression. Female CD rats (20 per group) received daily oral (gavage) exposure to TAM (0 or 60 microg/kg/day) and/or BEX (0, 5, 15, or 45 mg/kg/day) for a minimum of 90 days. BEX induced mild, dose-related anemia and dose-related increases in serum alkaline phosphatase, cholesterol, triglycerides, and calcium levels, and increased platelet counts. TAM had no biologically significant effect on any clinical pathology parameter and did not alter the effects of BEX on these endpoints. Microscopic alterations induced by BEX included epidermal hyperplasia, hyperkeratosis (stomach), and cytoplasmic clearing (liver). Microscopic changes in TAM-treated rats were limited to mucous cell hypertrophy in the cervix and vagina. The toxicity of administration of the combination of TAM + BEX can generally be predicted on the basis of the toxicity of each drug as a single agent. BEX induced dose-related alterations in the expression of several genes involved in steroid, drug, and/or fatty acid metabolism; TAM did not alter these effects of BEX. Differential expression of genes involved in drug and lipid metabolism may underlie the observed effects of BEX on cholesterol and triglyceride levels and its effects on liver histology.
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PMID:Subchronic toxicity and toxicogenomic evaluation of tamoxifen citrate + bexarotene in female rats. 1763 Apr 14

We report a case of advanced breast cancer with skin ulceration and bleeding (T4bN3bM0: Stage IIIC) achieving a significant improvement of QOL by toremifene and paclitaxel therapy. The patient was a 38-year-old woman with slight anemia who had ulcerative breast lump with skin ulcer. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma positive for estrogen receptor and progesteron receptor, and negative for HER2/neu protein expression. She received 6 cycles of tri-weekly FEC (C: 500 mg, E: 60 mg, F: 500 mg/m2) and 16 cycles of weekly paclitaxel (80 mg/m2) with toremifene (120 mg/day). The anemia and the bleeding from the tumor disappeared after FEC chemotherapy. The response for breast tumor after paclitaxel and toremifene therapy was evaluated as partial response, and the infraclavicular, subpectoral, and interpectoral lymph nodes metastasis disappeared. Muscle-preserving radical mastectomy (Bt + Ax: Auchincloss) with skin transplantation was performed. She had no recurrence during one year after the operation. Paclitaxel and Toremifene therapy was effective for advanced breast tumor, and can improve a patient QOL and the clinical outcomes in Stage IIIC advanced breast cancer.
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PMID:[A case of advanced breast cancer successfully treated with paclitaxel and toremifene therapy]. 1910 76


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